Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

BACKGROUND: Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. CASE PRESENTATION: In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. CONCLUSIONS: Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

Radiotherapy in Gorlin Syndrome: Can It Be Safe and Effective in Adult Patients?

Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare autosomal dominant disorder with multiple manifestations including early onset of cutaneous basal cell carcinomas (BCCs). Radiotherapy has traditionally been contraindicated due to reports of BCC induction. We describe here a patient treated successfully with radiotherapy with no tumour induction at 57 months of follow-up. A comprehensive literature review of radiotherapy outcomes in patients with Gorlin syndrome suggests radiotherapy may be a feasible treatment option for adult patients with treatment refractory lesions or surgical contraindication.

Methylaminolaevulinate photodynamic therapy in patients with multiple basal cell carcinomas in the setting of Gorlin-Goltz syndrome or after radiotherapy.

BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is a therapeutic challenge due to the multiplicity of cutaneous tumours. Photodynamic therapy (PDT) is increasingly used as an alternative treatment for superficial and in some countries nodular basal cell carcinomas (BCC). OBJECTIVE: To study the safety and efficiency of PDT in NBCCS. METHODS: We reviewed retrospectively the evolution of 62 lesions from patients with multiple BCC treated with PDT. RESULTS: The initial response rate (85.4%, 53/62) and recurrence rate (7.5%) appeared comparable to literature values in NBCCS and to those reported in the treatment of sporadic BCC. The clearance rate without recurrence was 79% (49/62), during a mean follow-up period of 13 months. The cosmetic outcome was excellent. Recurrences were found almost 2 years after treatment. CONCLUSION: PDT is a suitable therapeutic option in the management of NBCCS patients but requires a strict and long follow-up.

Treatment of basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple basal cell carcinomas (BCCs). A major problem for these patients is the enormous amount of BCCs which can invade in the deep underlying structures, especially in the face. Different treatment modalities are used in these patients; surgical excision, Mohs micrographic surgery, cryotherapy, photodynamic therapy, ablative laser therapy and topical 5% imiquimod. There is no evidence based advice how to treat a NBCCS patient. OBJECTIVE: To give a review of the literature about the possible treatment modalities for the multiple BCCs in NBCCS patients. RESULTS: Literature consists mainly of case reports; no evidence based advice how to treat a NBCCS patient exists. Multiple treatments are available (surgical and non-surgical), and a lot of them can be combined. Treatment in a megasession is an option to diminish the medical and social inconvenience for the patient.

Radiation-sensitive genetically susceptible pediatric sub-populations.

Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation.

Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes.

In recent years the use of radiation treatment for benign tumours has increased with the advent of stereotactic delivery and, in particular, single high dose gamma knife therapy. This has been particularly true for benign CNS (central nervous system) tumours such as vestibular schwannoma, meningioma, pituitary adenoma, and haemangioblastoma. While short term follow up in patients with isolated tumours suggests this treatment is safe, there are particular concerns regarding its use in childhood and in tumour predisposing syndromes. We have reviewed the use of radiation treatment in these contexts with particular regard to malignant transformation and new tumour induction. This review indicates that much more caution is warranted regarding the use of radiation treatment for benign tumours in childhood and in tumour prone conditions such as the neurofibromatoses.

Possibility of treating basal cell carcinomas of nevoid basal cell carcinoma syndrome with superficial x-ray therapy.

BACKGROUND: The nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome, is a rare dermatological disease inherited according to an autosomal dominant pattern. From the dermatological point of view, the most evident characteristic of the syndrome is the early onset of multiple basal cell carcinomas (BCCs). An ideal treatment of BCCs of the NBCCS does not exist. OBJECTIVE: To evaluate if in particular cases (e.g. poor general health conditions, previous multiple surgical excisions) radiotherapy may be useful, under the condition that it does not promote the onset of new BCCs and that the healing of irradiated lesions is normal. METHODS: A study on 3 patients with 17 BCCs treated with superficial radiotherapy is here reported. RESULTS: Complete remission without carcinogenic effects was reached in all treated lesions, with a mean follow-up of 30.35 months. CONCLUSION: In our opinion, such results suggest the possibility of a cautious application of superficial radiotherapy in selected cases of NBCCS.

Ultrapulse CO2 used for the successful treatment of basal cell carcinomas found in patients with basal cell nevus syndrome.

BACKGROUND: Basal cell nevus syndrome (BCNS) is an inherited condition marked by multiple basal cell carcinomas (BCCs) associated with several other abnormalities. Various treatment modalities have been used to eradicate these tumors. However, recurrences and scarring limit their use. OBJECTIVE: To evaluate the treatment of multiple BCCs associated with BCNS. METHODS: We describe three cases of BCNS in which multiple BCCs were effectively treated with ultrapulse CO2 laser. Postoperative Mohs micrographic surgical sections (thin sections looking for residual tumor) verified complete histologic clearance of the tumors. RESULTS: All three patients were effectively treated with ultrapulse CO2 laser. Minimal scarring was noted at follow-up. CONCLUSION: Ultrapulse CO2 laser can be used to effectively treat small BCCs in low-risk areas associated with BCNS with minimal posttreatment scarring.

Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to > 1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include "coarse face" in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the falx cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the affected individuals. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management.